“Controlled/living” radical polymerization (CRP) became one of the robust and powerful techniques for polymer synthesis, during the past decade. CRP can be achieved by creation of a dynamic equilibrium between a dormant species and propagating radicals via reversible deactivation or chain transfer procedures. This goal can be achieved by several recently developed controlled polymerization techniques available for review at [http://www.chem.cmu.edu/groups/maty/about/research/02.html] which include stable free-radical polymerization (SFRP) predominately nitroxide mediated polymerization (NMP), atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain transfer polymerization (RAFT), and Te, Sb, and Bi-mediate polymerization, reversible chain transfer catalyzed polymerization.
Since CRP processes generally provide compositionally homogeneous well-defined polymers (with predictable molecular weight, narrow molecular weight distribution, and high degree of chain end-functionalization) they have been the subject of much study. Progress in the different CRP procedures has been reported in several review articles, (ATRP) (See Matyjaszewski, K. ACS Symp. Ser. 1998, 685, 258-283; Matyjaszewski, K. ACS Symp. Ser. 2000, 768, 2-26; Qiu, J.; Charleux, B.; Matyjaszewski, K. Prog. Polym. Sci. 2001, 26, 2083-2134; Davis, K. A.; Matyjaszewski, K. Advances in Polymer Science 2002, 159, 2-166) nitroxide mediated polymerization (NMP), (See Hawker, C. J.; Bosman, A. W.; Harth, E. Chem. Rev. 2001, 101, 3661-3688) reversible addition fragmentation chain transfer (RAFT) (See Chiefari, J.; Chong, Y. K.; Ercole, F.; Krstina, J.; Jeffery, J.; Le, T. P. T.; Mayadunne, R. T. A.; Meijs, G. F.; Moad, C. L.; Moad, G.; Rizzardo, E.; Thang, S. H. Macromolecules 1998, 31, 5559-5562;Chiefari, J.; Rizzardo, E. In Handbook of Radical Polymerization; Matyjaszewski, K.; Davis, T. P., Eds.; Wiley-Interscience: Hoboken, 2002; pp 629-690; Moad, G.; Rizzardo, E.; Thang, S. H. Australian Journal of Chemistry 2005, 58, 379-410) and catalytic chain transfer (CCT) (See Gridnev, A. A.; Ittel, S. D. Chemical Reviews 2001, 101, 3611-3659.)
Each CRP process provides some advantages over the other procedures. One of the advantages of RAFT is that it can polymerize a broader range of radically copolymerizable monomers than NMP or ATRP under conditions typical of a standard free radical polymerization. Most of (conjugated and non-conjugated) vinyl monomers can be polymerized by this method. Various dithioesters, dithiocarbamates, trithiocarbonates and substituted xanthates (See Quiclet-Sire, B.; Zard, S. Z. Topics in Current Chemistry 2006, 264, 201-236) have been effectively used as transfer agents to control molecular weight, molecular weight distribution, and molecular architecture of polymeric materials prepared from a wide range of monomers. The simplified mechanism involves, in addition to initiation, propagation, and termination, typical of a conventional radical polymerization, a series of reversible addition-fragmentation chain transfer steps between the CTA and a radical. (See Chiefari, J.; Chong, Y. K.; Ercole, F.; Krstina, J.; Jeffery, J.; Le, T. P. T.; Mayadunne, R. T. A.; Meijs, G. F.; Moad, C. L.; Moad, G.; Rizzardo, E.; Thang, S. H. Macromolecules 1998, 31, 5559-5562; Goto, A.; Fukuda, T. Progress in Polymer Science 2004, 29, 329-385.) The exchange reaction process repeats itself many times so that every chain has a similar chance to grow. One limitation of RAFT polymerization is that the procedure requires the presence of a conventional radical initiator or other source of radicals such as peroxides or percarbonates in addition to a monomer and a chain transfer agent (CTA) in the reaction medium the final product contains a low fraction of radical initiated polymers. A need therefore exists for a manner to prepare materials with lower fractions of side products. Another limitation of RAFT and MADIX controlled transfer polymerization processes are that there is no universal transfer agent and many different transfer agents have to be prepared to optimally polymerize the full spectrum of radically copolymerizable monomers. Furthermore there was no universal efficient procedure to prepare the desired transfer agents.
Matyjaszewski and coworkers disclosed the fundamental four component Atom Transfer Radical Polymerization (ATRP) process comprising the addition, or in situ formation, of an initiator, in this case a molecule with a transferable atom or group that is completely incorporated into the final product, a transition metal and a ligand that form, a partially soluble transition metal complex that participates in a reversible redox reaction with the added initiator or a dormant polymer to form the active species to copolymerize radically polymerizable monomers, and a number of improvements to the basic ATRP process, in a number of commonly assigned patents and patent applications: U.S. Pat. Nos. 5,763,546; 5,807,937; 5,789,487; 5,945,491; 6,111,022; 6,121,371; 6,124,411; 6,162,882; 6,624,262; 6,407,187; 6,512,060; 6,538,091; 6,541,580; 6,624,262 ; 6,627,314; 6,759,491 ; 6,790,919; 6,887,962; 7,019,082; 7,049,373; 7,064,166; 7,125,938 ; 7,157,530; 7.332,550 and U.S. patent application Ser. Nos. 09/534,827; PCT/US04/09905; PCT/US05/007264; PCT/US05/007265; PCT/US06/33152; PCT/US2006/048656 and PCT/US08/64710, all of which are herein incorporated by reference.
ATRP is the most efficient CRP methods for the preparation of pure segmented copolymers, since it does not require addition of a radical initiator to continuously form new polymer chains, allowing the synthesis of novel multi-segmented copolymers with a predetermined degree of polymerization, low molecular weight distribution (Mw/Mn), incorporating a wide range of functional monomers and displaying controllable macromolecular structures under mild reaction conditions. ATRP generally requires addition of formation or an alkyl halide or (pseudo)halide as an initiator (R—X) or dormant polymer chain end (Pn—X), and a partially soluble transition metal complex (Cu, Fe or Ru, for example) capable of undergoing a redox reaction as a catalyst. As shown in Scheme 1 ATRP involves homolytic cleavage of the Pn—X bond by a transition metal complex (Cu1—X/L) (with a rate constant kact), followed by propagation (with rate constant kp) and reversible deactivation of the propagating chain radical (Pn*) (with a rate constant kdeact) by repetitive transfer of the halogen or pseudo-halogen atom from and to the transition metal complex. The polymer grows by insertion of the monomer(s) present in the reaction medium between the Pn— and —X bond.

Iniferter polymerization, which was disclosed in 1982 by Otsu and coworkers, (See Otsu, T.; Yoshida, M.; Tazaki, T. Makromol. Chem., Rapid Commun. 1982, 3, 133-140; Otsu, T.; Yoshida, M.; Kuriyama, A. Polym. Bull. 1982, 7, 45-50) was one of the earliest attempts to develop a CRP technique. Suitable iniferters developed in the next two decades included diphenyl disulfide, tetraethylthiuram disulfide, benzyl diethyldithiocarbamate and 2-phenylethyl diethyldithiocarbamate. The propagating polymer chain end was always the Et2NCSS— group, which can photo-dissociate into a reactive propagating radical and a less reactive small radical Et2NCSS* resulting in successive insertion of monomers into the dissociated bond. However, the structures and compositions of the polymers were poorly controlled and the polymers displayed relatively high polydispersity (PDI).
Some improvements in iniferter polymerization were made in the presence of copper catalyst. When the reverse ATRP of methyl methacrylate (MMA) was carried out in the presence of copper(II) N,N-diethyldithiocarbamate, poly(methyl methacrylate) (PMMA) with relatively narrow molecular weight distribution was obtained but the initiation efficiency was low and a large amount of radical initiator was used, resulting in a high level of chain termination. (See Li, P.; Qiu, K.-Y. Journal of Polymer Science, Part A: Polymer Chemistry 2002, 40, 2093-2097; Li, P.; Qiu, K.-Y. Living and Controlled Polymerization: Synthesis, Characterization and Properties of the Respective Polymers and Copolymers 2006, 39-50.) Also, when normal ATRP of MMA and styrene (St) was initiated by ethyl 2-N,N-(diethylamino)dithiocarbamoyl-butyrate and (1-naphthyl)-methyl N,N-diethyldithiocarbamate, low initiation efficiency and relatively low molecular weight PMMA and polystyrene (PSt) were formed. (See Zhang, W.; Zhu, X.; Zhu, J.; Chen, J. Journal of Polymer Science, Part A: Polymer Chemistry 2005, 44, 32-41.)
As discussed below these prior art ATRP/dithiocarbamate systems do not comprise transfer agents with the preferred structure selected for each monomer as disclosed herein nor when employed as ATRP initiators form polymers with targeted high molecular weight.
There are examples of using photo-initiated polymerization in free radical polymerization but there are only a few reports in which light is utilized for CRP. One of those examples is iniferter polymerization. Nevertheless, as noted above many of polymers prepared by the iniferter technique showed high polydispersity, poor initiation efficiency, and much higher molecular weight (MW) than theoretical values. The other polymerization process where a few cases of photo-initiation was examined is RAFT polymerization and these examples also realized only limited success. (See Lu, L.; Zhang, H.; Yang, N.; Cai, Y. Macromolecules 2006, 39, 3770-3776.)
Therefore, as disclosed in one embodiment of the invention, developing polymerization methods which adopt the advantages of photo-iniferter and ATRP (or other CRP procedures) will bring variety of options for designing novel polymeric materials. Particularly, precise photo-patterning of materials on a substrate can be conducted in a much simpler way by photoinitiated polymerization of polymers with desired properties from precisely defined photo-stimulated areas using the novel technique disclosed.
As noted above RAFT polymerizations process require a continuous supply of new initiating radicals by the decomposition of radical initiators (I2 in Scheme 2), such as AIBN, to activate the process and to compensate for radical/radical chain termination between propagating radicals. During the first stages of the polymerization the RAFT agent (ZC═SSR) is consumed by propagating radicals by an addition-fragmentation mechanism. The fragmented radical (R.) reinitiates polymerization, resulting in new propagating radicals which then take part in the equilibrium established between the dormant polymer and active chains.

However since the radical initiators in the RAFT system produce new polymer chains they decrease chain end functionality. Therefore, it is difficult to prepare pure telechelic (co)polymers or pure block copolymers or high molecular weight polymers with narrow polydispersity, especially at higher radical initiator concentrations.
In one embodiment of the present invention these aforementioned problems are resolved using transition metal-catalyzed RAFT polymerization (which does not require addition of any conventional initiator) producing purer block copolymers and high molecular weight polymers in a well-controlled manner. If one focuses on the mechanism the procedure can be thought of as a transition metal mediated chain transfer agent (CTA) polymerization. As discussed below (in scheme 6) the developed procedure is also applied to formation of CTAs with a range of Z-groups and R-groups suitable for polymerization of the full spectrum of radically copolymerizable monomers as illustrated in Scheme 3. (See Moad, G.; Rizzardo, E.; Thang, S. H. Acc. Chem. Res. 2008, 41, 1133-1142.) The procedure is readily adaptable to form multi-functional transfer agents for preparation ABA and (AB)n star copolymers.

Z-addition rates decrease and fragmentation rates increase from left to right whereas for R-fragmentation rates decrease from left to right. Stabilizing Z groups such as -Ph and -Me are efficient in styrene and methacrylate polymerization, but they retard polymerization of acrylates and inhibit polymerization of vinyl esters. Weakly stabilizing groups, such as —NR2 in dithiocarbamates or —OR in xanthates, are good for vinyl esters, vinyl pyrrolidones (NVP) and vinyl carbazoles (NVC) but inefficient for styrene. Therefore for activation of CTAs by Cu complexes, while R groups as reactive as, or more reactive than styryl should work the proper selection of the Z- and R-groups of the CTA as well as the appropriate selection of a monomer for a particular CTA is a determinant for a successful transition metal mediated RAFT polymerization and ATRP involving appropriately selected transition metal complex transferable dithio-derivatives as initiators. Indeed this combination of CRP procedures could be considered to be closely linked as comprising a transition metal mediated degenerative chain transfer polymerization. The selection of the R-group should take into account the stability of the dormant species and the rate of addition of R. to a given monomer. The order of R-group leaving ability reflects the importance of both steric and electronic effects. Steric effects in RAFT are much more important than in ATRP. Therefore there are differences between the functionality that should be selected for the Z-group for the agent to be employed in an “ATRP” involving appropriately selected transition metal complex transferable dithio-derivatives and a transition metal mediated “RAFT” polymerization. In an “ATRP” a secondary 2-bromopropionitrile is more reactive than tertiary 2-bromoisobutyrate while in a “RAFT” polymerization it is the reverse situation.
Suitable transfer agents with a range of Z- and —R functional groups have been detailed in WO 98/01478 and WO/9858974, including U.S. Pat. No. 6,153,705, and in recent review articles (See Quiclet-Sire, B.; Zard, S. Z. Topics in Current Chemistry 2006, 264, 201-236; Moad, G.; Rizzardo, E.; Thang, S. H. Polymer 2008, 49, 1079-1131; Taton, D.; Destarac, M.; Zard, S. Z. Title: Handbook of RAFT Polymerization 2008, 373-421) which are hereby incorporated to illustrate the range of Z- and —R functional groups that can be selected for this novel transition metal mediated chain transfer agent polymerization.
Currently RAFT agents are synthesized in moderate-to-excellent yields by several methods:
(1) Reaction of a carbodithioate salt with an alkylating agent. (See Chong, Y. K.; Krstina, J.; Le, T. P. T.; Moad, G.; Postma, A.; Rizzardo, E.; Thang, S. H. Macromolecules 2003, 36, 2256-2272; Chiefari, J.; Mayadunne, R. T. A.; Moad, C. L.; Moad, G.; Rizzardo, E.; Postma, A.; Skidmore, M. A.; Thang, S. H. Macromolecules 2003, 36, 2273-2283; Le, T. P.; Moad, G.; Rizzardo, E.; Thang, S. H. In PCT Int. Appl.; (E.I. Du Pont De Nemours and Co., USA; Le, Tam Phuong; Moad, Graeme; Rizzardo, Ezio; Thang, San Hoa). WO1998/01478, 1998; p 88 pp.)
(2) Addition of a dithio acid across an olefinic double bond. (See Chong, Y. K.; Krstina, J.; Le, T. P. T.; Moad, G.; Postma, A.; Rizzardo, E.; Thang, S. H. Macromolecules 2003, 36, 2256-2272.)
(3) Radical-induced decomposition of a bis(thioacyl) disulfide. (See Rizzardo, E.; Thang, S. H.; Moad, G. In PCT Int. Appl.; (Commonwealth Scientific and Industrial Research Organisation, Australia; E.I. Du Pont De Nemours and Company). WO 99/05099, 1999; p 40 pp.)
(4) Sulfuration of a thioloester, (See Chong, Y. K.; Krstina, J.; Le, T. P. T.; Moad, G.; Postma, A.; Rizzardo, E.; Thang, S. H. Macromolecules 2003, 36, 2256-2272; Le, T. P.; Moad, G.; Rizzardo, E.; Thang, S. H. In PCT Int. Appl.; (E.I. Du Pont De Nemours and Co., USA; Le, Tam Phuong; Moad, Graeme; Rizzardo, Ezio; Thang, San Hoa). WO1998/01478, 1998; p 88 pp.) a carboxylic acid with an alcohol, and treatment of carboxylic acid with P4S10.
(5) Radical-induced ester exchange. (See Chong, Y. K.; Krstina, J.; Le, T. P. T.; Moad, G.; Postma, A.; Rizzardo, E.; Thang, S. H. Macromolecules 2003, 36, 2256-2272.)
(6) Reaction of thiocarbonylbisimidazole with thiol or alcohol. However, all the methods reported above require a tedious purification process which adds cost to the final material.
A significant improvement would be attained if desired monomer specific mono-functional or multi-functional RAFT agents could be obtained in high yields and used directly in the polymerization reaction without any further purification.
Disclosed herein is a broadly applicable process for synthesis and use of various new iniferter/ATRP initiators containing a series of different dithiocarbamate (DC) and trithiocarbonate (TTC) structures and their successful introduction into ATRP by determining which initiators and catalyst complexes interact together to form active polymerization mediators that can produce exemplary well-defined low PDI polymers. Since the DC group can be activated by UV irradiation, this class of initiators can also be employed as photo-initiators resulting in a procedure for photo-initiated ATRP and as transfer agents in the novel disclosed transition metal initiated RAFT polymerizations.
As noted above reversible addition—fragmentation chain transfer (RAFT) polymerization is that it can be used for a wider range of functional and nonfunctional monomers. In RAFT polymerization, the activation deactivation equilibrium is a chain transfer reaction. Radicals are neither formed nor destroyed in these steps and maintain polymerization in the absence of termination reactions. However, since termination reactions are unavoidable in radical polymerization processes the RAFT process requires a constant radical source (generally from decomposition of a standard radical initiator) to maintain an active chain transfer reaction. Therefore, initiation and bimolecular termination reactions occur as in conventional radical polymerization and pure telechelic-functional copolymers are not formed.
Normal ATRP procedures do not require an added free radical initiator as in the RAFT polymerization since the first radical is formed in a redox transfer reaction with an added transition metal catalyst therefore development of a new controlled polymerization method combining aspects of RAFT and ATRP would be a process improvement of value to both procedures. In other words, if one can perform a RAFT polymerization, not by adding a radical initiator but by generating the propagating radical from the added RAFT agent itself by reaction with a transition metal catalyst, thereby allowing one to prepare purer (block)polymers this is an improvement. Similarly if one can expand the range of monomers polymerizable by transition metal mediated chain transfer agent (CTA) polymerization this is an improvement.
Embodiments of this disclosure demonstrate methodology to prepare well defined pure segmented copolymers further comprising segments incorporating non-conjugated vinyl monomers. Other embodiments allow procedures for preparation of mono- and multi-functional initiators for controlled radical polymerization reactions. Still other embodiments allow combination of ATRP and RAFT polymerization procedures in sequential or concurrent copolymerization reactions to form novel segmented copolymers and high molecular weight copolymers with site specific functionality.